2(R)-4-Oxo-4-[3-(trifluoromethyl)-5,6-dihydro[1,2,4]triazolo[4,3-a]-7(8H)-pyrazinyl]-1-(2,4,5-trifluorophenyl)-2-butanamine, namely Sitagliptin, having the following formula

is used in the form of the phosphate monohydrate salt in the treatment of diabetes mellitus of Type II
U.S. Pat. No. 6,699,871 discloses the synthesis of Sitagliptin according to the scheme reported below. In particular, the protected β-amino acid of formula (A) is coupled with an amine of formula (B) in the presence of a carbodiimide (EDC), hydroxybenzotriazole (HOBT), diisopropylethylamine (DIPEA) and dimethylformamide (DMF) to obtain a compound of formula (C) which is converted to Sitagliptin by deprotection of the amine function.

U.S. Pat. No. 6,699,871 also discloses the preparation of the β-amino acid compound (A) and of the amine (B) hydrochloride. In particular, the preparation of the β-amino acid compound (A) is carried out starting from corresponding α-amino acid by Arndt-Eistert homologation reaction with diazomethane, a toxic and explosive reagent. Said process is hardly applicable on an industrial scale due to the high cost of the intermediates used and the safety problems the use of diazomethane involves.
WO 2005/097733 and WO 2006/081151 disclose the preparation of Sitagliptin by stereoselective catalytic hydrogenation of a β-amino acrylamide. This kind of process is also affected with important problems concerning industrial applicability, due to the high cost of intermediates such as 2,4,5-trifluorophenylacetic acid and 2,2-dimethyl-1,3-dioxane-4,6-dione (Meldrum's acid). Furthermore, the stereoselective catalytic hydrogenation of the β-amino acrylamide is carried out using sophisticated and fragile Rh(I) complexes in the presence of expensive diphosphine ligands, which prevent their applicability on an industrial scale.
As can be appreciated these processes involve the use of either toxic, dangerous reagents such as diazomethane, or difficult and costly to prepare starting materials or complex catalytic systems which consequently remarkably affect costs. There is therefore the need for an alternative synthetic route which provides Sitagliptin or a salt thereof, having high enantiomeric and chemical purity, starting from low cost starting materials.